Home LiteratureArticle Details
PMID: 9261384 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Epstein-Barr virus leader protein enhances EBNA-2-mediated transactivation of latent membrane protein 1 expression: a role for the W1W2 repeat domain.

Journal of virology ·Vol. 71 ·No. 9 ·1997-09-00 ·Pages 6619-28

Nitsche F, Bell A, Rickinson A

Abstract

The Epstein-Barr virus (EBV)-encoded leader protein EBNA-LP is made up of several 66-amino-acid repeats (the W1W2 domains) linked to a unique 45-amino-acid C-terminal sequence (the Y1Y2 domain). This protein is highly expressed along with a second nuclear antigen, EBNA-2, during the initial stages of virus-induced B-cell transformation. While EBNA-2's essential role in transformation as a transcriptional activatory is well documented, very little is known about EBNA-LP function except that recombinant viruses lacking the EBNA-LP Y1Y2 exons show reduced, but still detectable, transforming ability. This was taken as evidence that EBNA-LP plays an auxiliary role but is not essential for transformation. A recent study showed that EBNA-LP could cooperate with EBNA-2 in activating cyclin D2 transcription in resting B cells (A.J. Sinclair, L Palmero, G. Peters, and P.J. Farrell, EMBO J. 13:3321-3328, 1994). Here we report that EBNA-LP can also cooperate with EBNA-2 in up-regulating expression of the major EBV effector protein of B-cell transformation, latent membrane protein 1 (LMP1). In transient-transfection assays, EBNA-LP enhanced the level of EBNA-2-induced LMP1 expression by 5- to 10-fold in one Latency I Burkitt's lymphoma cell line, Eli-BL, and was absolutely required, along with EBNA-2, to induce LMP1 in a second line, Akata-BL. These changes in LMP1 protein expression appeared to be reflected at the transcriptional level. A study of EBNA-LP mutants showed that this cooperative function mapped to the W1W2 repeat domain rather than to Y1Y2. Because a Y1Y2-deleted form of EBNA-LP may therefore retain some aspects of wild-type function, the original data from virus recombinants leave open the possibility that EBNA-LP is actually an essential transforming gene.

MeSH Terms
Amino Acid Sequence Epstein-Barr Virus Nuclear Antigens/biosynthesis,genetics,metabolism Gene Expression Regulation, Viral Herpesvirus 4, Human/genetics,metabolism Humans Mutagenesis, Insertional RNA, Messenger Transcriptional Activation Transfection Tumor Cells, Cultured Viral Matrix Proteins/biosynthesis,genetics
Chemicals
EBV-associated membrane antigen, Epstein-Barr virus Epstein-Barr Virus Nuclear Antigens RNA, Messenger Viral Matrix Proteins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Nitsche F
CRC Institute for Cancer Studies, University of Birmingham, United Kingdom.
Bell A
Rickinson A
References (54)
54 references, click to expand
  1. Epstein-Barr virus latent membrane protein 1 is essential for B-lymphocyte growth transformation.
    Proc Natl Acad Sci U S A. 1993 Oct 1;90(19):9150-4 PMID: 8415670
  2. Epstein-Barr virus nuclear protein 2 is a key determinant of lymphocyte transformation.
    Proc Natl Acad Sci U S A. 1989 Dec;86(23):9558-62 PMID: 2556717
  3. EBNA-2 and EBNA-LP cooperate to cause G0 to G1 transition during immortalization of resting human B lymphocytes by Epstein-Barr virus.
    EMBO J. 1994 Jul 15;13(14):3321-8 PMID: 8045261
  4. The Epstein-Barr virus nuclear antigen 2 transactivator is directed to response elements by the J kappa recombination signal binding protein.
    Proc Natl Acad Sci U S A. 1994 Aug 2;91(16):7568-72 PMID: 8052621
  5. Identification and characterization of an Epstein-Barr virus nuclear antigen 2-responsive cis element in the bidirectional promoter region of latent membrane protein and terminal protein 2 genes.
    J Virol. 1994 Nov;68(11):6947-58 PMID: 7933076
  6. Epstein-Barr virus nuclear antigen 2 exerts its transactivating function through interaction with recombination signal binding protein RBP-J kappa, the homologue of Drosophila Suppressor of Hairless.
    EMBO J. 1994 Oct 17;13(20):4973-82 PMID: 7957063
  7. HSV-1 IE protein Vmw110 causes redistribution of PML.
    EMBO J. 1994 Nov 1;13(21):5062-9 PMID: 7957072
  8. Immortalization of human B lymphocytes by a plasmid containing 71 kilobase pairs of Epstein-Barr virus DNA.
    J Virol. 1995 Jan;69(1):231-8 PMID: 7983714
  9. Epstein-Barr virus nuclear protein 2 transactivation of the latent membrane protein 1 promoter is mediated by J kappa and PU.1.
    J Virol. 1995 Jan;69(1):253-62 PMID: 7983717
  10. Cell growth effects of Epstein-Barr virus leader protein.
    J Gen Virol. 1992 Jun;73 ( Pt 6):1547-51 PMID: 1318948
  11. Epstein-Barr virus nuclear proteins EBNA-3A and EBNA-3C are essential for B-lymphocyte growth transformation.
    J Virol. 1993 Apr;67(4):2014-25 PMID: 8445720
  12. EBNA-5, an Epstein-Barr virus-encoded nuclear antigen, binds to the retinoblastoma and p53 proteins.
    Proc Natl Acad Sci U S A. 1993 Jun 15;90(12):5455-9 PMID: 8390666
  13. Stable transfection of Epstein-Barr virus (EBV) nuclear antigen 2 in lymphoma cells containing the EBV P3HR1 genome induces expression of B-cell activation molecules CD21 and CD23.
    J Virol. 1990 Mar;64(3):1002-13 PMID: 2154588
  14. Promoter switching in Epstein-Barr virus during the initial stages of infection of B lymphocytes.
    Proc Natl Acad Sci U S A. 1990 Mar;87(5):1725-9 PMID: 2155423
  15. Epstein-Barr virus nuclear antigen 2 induces expression of the virus-encoded latent membrane protein.
    J Virol. 1990 May;64(5):2126-34 PMID: 2157875
  16. Epstein-Barr virus latent membrane protein (LMP1) and nuclear proteins 2 and 3C are effectors of phenotypic changes in B lymphocytes: EBNA-2 and LMP1 cooperatively induce CD23.
    J Virol. 1990 May;64(5):2309-18 PMID: 2157887
  17. Subnuclear localization and phosphorylation of Epstein-Barr virus latent infection nuclear proteins.
    Virology. 1990 Jun;176(2):563-74 PMID: 2161150
  18. Epstein-Barr virus nuclear antigen 2 transactivates latent membrane protein LMP1.
    J Virol. 1990 Jul;64(7):3407-16 PMID: 2352328
  19. Epstein-Barr virus nuclear antigen 2 activates transcription of the terminal protein gene.
    J Virol. 1991 Jan;65(1):415-23 PMID: 1845900
  20. Early events in Epstein-Barr virus infection of human B lymphocytes.
    Virology. 1991 Apr;181(2):595-608 PMID: 1849678
  21. EBNA-2 transactivates a lymphoid-specific enhancer in the BamHI C promoter of Epstein-Barr virus.
    J Virol. 1991 May;65(5):2164-9 PMID: 1850003
  22. Induction of bcl-2 expression by Epstein-Barr virus latent membrane protein 1 protects infected B cells from programmed cell death.
    Cell. 1991 Jun 28;65(7):1107-15 PMID: 1648447
  23. The Epstein-Barr virus nuclear protein encoded by the leader of the EBNA RNAs is important in B-lymphocyte transformation.
    J Virol. 1991 Dec;65(12):6826-37 PMID: 1658376
  24. Co-localization of the retinoblastoma protein and the Epstein-Barr virus-encoded nuclear antigen EBNA-5.
    Exp Cell Res. 1991 Dec;197(2):314-8 PMID: 1659990
  25. Epstein-Barr virus latent gene transcription in nasopharyngeal carcinoma cells: coexpression of EBNA1, LMP1, and LMP2 transcripts.
    J Virol. 1992 May;66(5):2689-97 PMID: 1313894
  26. Use of second-site homologous recombination to demonstrate that Epstein-Barr virus nuclear protein 3B is not important for lymphocyte infection or growth transformation in vitro.
    J Virol. 1992 May;66(5):2893-903 PMID: 1313908
  27. The Epstein-Barr virus transforming protein LMP1 engages signaling proteins for the tumor necrosis factor receptor family.
    Cell. 1995 Feb 10;80(3):389-99 PMID: 7859281
  28. Epstein-Barr virus nuclear protein 3C modulates transcription through interaction with the sequence-specific DNA-binding protein J kappa.
    J Virol. 1995 May;69(5):3108-16 PMID: 7707539
  29. Epstein-Barr virus nuclear antigen 3C is a transcriptional regulator.
    J Virol. 1995 Jun;69(6):3624-30 PMID: 7745710
  30. Resting B-cells, EBV-infected B-blasts and established lymphoblastoid cell lines differ in their Rb, p53 and EBNA-5 expression patterns.
    Oncogene. 1995 May 4;10(9):1869-74 PMID: 7753563
  31. Restoration of endogenous antigen processing in Burkitt's lymphoma cells by Epstein-Barr virus latent membrane protein-1: coordinate up-regulation of peptide transporters and HLA-class I antigen expression.
    Eur J Immunol. 1995 May;25(5):1374-84 PMID: 7774641
  32. Epstein-Barr virus EBNA-LP and transcription regulation properties of pRB, p107 and p53 in transfection assays.
    J Gen Virol. 1995 Sep;76 ( Pt 9):2141-9 PMID: 7561751
  33. Targeting of adenovirus E1A and E4-ORF3 proteins to nuclear matrix-associated PML bodies.
    J Cell Biol. 1995 Oct;131(1):45-56 PMID: 7559785
  34. Reversible nucleolar translocation of Epstein-Barr virus-encoded EBNA-5 and hsp70 proteins after exposure to heat shock or cell density congestion.
    J Gen Virol. 1995 Oct;76 ( Pt 10):2423-32 PMID: 7595346
  35. The Epstein-Barr virus nuclear antigen leader protein associates with hsp72/hsc73.
    J Virol. 1995 Dec;69(12):8169-72 PMID: 7494344
  36. The Epstein-Barr virus-encoded nuclear antigen EBNA-5 accumulates in PML-containing bodies.
    J Virol. 1996 Apr;70(4):2562-8 PMID: 8642686
  37. The amino-terminal domains of Epstein-Barr virus nuclear proteins 3A, 3B, and 3C interact with RBPJ(kappa).
    J Virol. 1996 May;70(5):3068-74 PMID: 8627785
  38. Protein-protein interactions between Epstein-Barr virus nuclear antigen-LP and cellular gene products: binding of 70-kilodalton heat shock proteins.
    Virology. 1996 Jun 1;220(1):91-9 PMID: 8659132
  39. A conserved domain of the Epstein-Barr virus nuclear antigens 3A and 3C binds to a discrete domain of Jkappa.
    J Virol. 1996 Jul;70(7):4228-36 PMID: 8676443
  40. Cell cycle stage-specific phosphorylation of the Epstein-Barr virus immortalization protein EBNA-LP.
    J Virol. 1996 Nov;70(11):7885-93 PMID: 8892911
  41. Epstein-Barr virus nuclear protein LP stimulates EBNA-2 acidic domain-mediated transcriptional activation.
    J Virol. 1997 Sep;71(9):6611-8 PMID: 9261383
  42. A cis-acting element from the Epstein-Barr viral genome that permits stable replication of recombinant plasmids in latently infected cells.
    Proc Natl Acad Sci U S A. 1984 Jun;81(12):3806-10 PMID: 6328526
  43. Nucleotide sequences of mRNAs encoding Epstein-Barr virus nuclear proteins: a probable transcriptional initiation site.
    Proc Natl Acad Sci U S A. 1986 Jul;83(14):5096-100 PMID: 3460083
  44. Endemic Burkitt's lymphoma: phenotypic analysis of tumor biopsy cells and of derived tumor cell lines.
    J Natl Cancer Inst. 1986 Sep;77(3):681-7 PMID: 2943927
  45. A bicistronic Epstein-Barr virus mRNA encodes two nuclear proteins in latently infected, growth-transformed lymphocytes.
    J Virol. 1987 Apr;61(4):945-54 PMID: 3029429
  46. Monoclonal antibodies to the latent membrane protein of Epstein-Barr virus reveal heterogeneity of the protein and inducible expression in virus-transformed cells.
    J Gen Virol. 1987 Jun;68 ( Pt 6):1575-86 PMID: 2438376
  47. Differences in B cell growth phenotype reflect novel patterns of Epstein-Barr virus latent gene expression in Burkitt's lymphoma cells.
    EMBO J. 1987 Sep;6(9):2743-51 PMID: 2824192
  48. Monoclonal and polyclonal antibodies against Epstein-Barr virus nuclear antigen 5 (EBNA-5) detect multiple protein species in Burkitt's lymphoma and lymphoblastoid cell lines.
    J Virol. 1987 Dec;61(12):3870-8 PMID: 2824821
  49. Different patterns of Epstein-Barr virus gene expression and of cytotoxic T-cell recognition in B-cell lines infected with transforming (B95.8) or nontransforming (P3HR1) virus strains.
    J Virol. 1988 Mar;62(3):894-901 PMID: 2828684
  50. A versatile in vivo and in vitro eukaryotic expression vector for protein engineering.
    Nucleic Acids Res. 1988 Jan 11;16(1):369 PMID: 3340539
  51. Synchronous and sequential activation of latently infected Epstein-Barr virus genomes.
    J Virol. 1989 Jan;63(1):445-9 PMID: 2462063
  52. Genetic analysis of immortalizing functions of Epstein-Barr virus in human B lymphocytes.
    Nature. 1989 Aug 3;340(6232):393-7 PMID: 2547164
  53. Expression of Epstein-Barr virus transformation-associated genes in tissues of patients with EBV lymphoproliferative disease.
    N Engl J Med. 1989 Oct 19;321(16):1080-5 PMID: 2552313
  54. Mediation of Epstein-Barr virus EBNA2 transactivation by recombination signal-binding protein J kappa.
    Science. 1994 Jul 1;265(5168):92-5 PMID: 8016657
Article Info
Journal
Journal of virology
Abbr.
J Virol
ISSN
0022-538X
DOI
10.1128/JVI.71.9.6619-6628.1997
Published
1997-09-00
Pages
6619-28
Language
English
Region
United States
NLM ID
0113724
PMCID
PMC191940
Subset
IM
External Links
PubMed source DOI: 10.1128/JVI.71.9.6619-6628.1997 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: [email protected]

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2